More than 5 million individuals in the United States have clinically manifest Heart Failure (HF), and that number continues to rise with the country's aging population, contributing to serious strains on our healthcare system and to huge economic costs. Diagnosing and managing the cardiovascular health concerns for such a large population, particularly the elderly who often also suffer from diabetes, has created a growing need for new healthcare technologies that will help: (1) accommodate the physical challenges of aging and diabetic HF patients and (2) lower medical cost and the strain on healthcare resources. Elevated levels of natriuretic peptide biomarkers NT-proBNP and BNP indicate the presence of myocardial stress, and in people with HF, these have been shown to correlate with acute exacerbations of this condition. Quantitation of natriuretic peptide levels is critical to th determination of appropriate emergency and clinical treatment, and currently the only blood-based assay that exists for the diagnosis of myocardial stress and management of HF. Studies where natriuretic peptides were used to guide drug therapies and diagnostics suggest reduced mortality and a significantly lowered number and duration of hospital stays, and that there is additional prognostic value of establishing an individual's baseline level of NT-proBNP. This simple, effective means of monitoring and diagnosis of cardiovascular health, combined with a technologically accurate and demographically relevant means of testing for a robust HF biomarker, presents a simple and compelling opportunity to provide support for the growing population of aging, diabetic HF patients. Our approach to sensor design is somewhat risky, and though our preliminary results are encouraging, we hope to use the R21 mechanism to unambiguously demonstrate quantitative NT-proBNP assay efficacy on an inexpensive electrochemical sensor with an LOD of <1 nM within 5 minutes in buffer (Aim 1). This will be followed in Aim 2 by buffer-based optimization studies with the goal of obtaining a dynamic NT-proBNP detection range of 53 - 212 pM (450 - 1,800 pg/mL). We will also determine coefficients of variation (CVs) and device stability at this stage. Once we are confident of NT-proBNP assay efficacy in buffer, we will then proceed to Aim 3, optimizing the assay in spiked, pooled human plasma and spiked, pooled human whole blood. If this project is successful, we will expand it to a more resource-intensive R01 study that will include: design and development of a reader and patient-user interface, development of data analysis and communication software to transmit results between patient and physician, and conduct of trials to evaluate the effectiveness of the device and its interface. Our ultimate goal is to create a means for HF patients to monitor a key cardiac biomarker at home for the first time. The opportunity to improve clinical decision-making, especially in relation to hospitalization and return to the community, directly addresses the NIH mission to improve quality of care, reduce costs, and to more closely couple physiological changes to medical intervention.